# Magnetothermal brain stimulation towards the rescue of beta-amyloid pathology

> **NIH NIH R01** · KENT STATE UNIVERSITY · 2022 · $377,200

## Abstract

Project Summary
Alzheimer's disease (AD) is a devastating neurodegenerative disorder and the first cause of dementia. Many
lines of genetic and biochemical evidence strongly highlight a pathological role of beta-amyloid (Aβ) where
extracellular deposition of amyloid plaques contributes to the loss of synapses and neurons, resulting in cognitive
deficits and eventually dementia. As such, the search for disease-modifying therapies for AD has been focused
on targeting the hallmark of the disease. Currently, there is no proven pharmacological treatment for preventing
the plaques once Aβ forms a larger aggregate and thus there is an urgent need to develop an innovative and
alternative strategy to clear Aβ plaques in the AD brain for the treatment of AD. Our long-term goal is to develop
a minimally invasive, non-pharmacological intervention to remove toxic Aβ plaques towards the treatment of AD.
To this end, herein we propose to apply magnetothermal brain stimulation as a non-pharmacological strategy to
target and remove toxic Aβ plaques towards the rescue of Aβ pathology. The principal of this approach is to
translate the energy of the high frequency alternating magnetic field (AMF) into thermal energy using
superparamagnetic nanoparticles (MNPs) as a transducer that can trigger thermo-mechanical and biological
signal with high temporal and spatial specificity. Our central hypothesis is that magnetothermal brain stimulation
facilitates Aβ clearance and improves cognitive function via heat shock protein 70 (HSP70) signaling in the AD
brain. This hypothesis is based on our published data demonstrating the feasibility of this approach in targeting
Aβ plaques where we showed that MNP/AMF-induced thermo-mechanical energy, applied within a safe
threshold for brain tissue, was sufficient to direct the disruption of Aβ fibrils into smaller fragments, which were
then readily phagocytosed and cleared by microglia. In our preliminary study, we also found that the remotely
stimulated thermal energy directed to human microglia could trigger biological signal that shifts microglial
activation towards improved Aβ clearance via HSP70-dependent manner. To prove our hypothesis, we propose
to (1) establish the threshold safe thermal dose of magnetothermal brain stimulation for brain functioning in mice,
(2) develop strategies for targeted magnetothermal brain stimulation towards the improved clearance of Aβ
plaques, and (3) investigate the cellular mechanism by which magnetothermal brain stimulation influences Aβ
pathology. The successful completion of the proposed study will provide detailed knowledge of how to apply
magnetothermal brain stimulation as an innovative therapeutic strategy against Aβ-mediated pathology in AD.

## Key facts

- **NIH application ID:** 10420096
- **Project number:** 1R01AG076699-01
- **Recipient organization:** KENT STATE UNIVERSITY
- **Principal Investigator:** Min Ho Kim
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $377,200
- **Award type:** 1
- **Project period:** 2022-05-15 → 2027-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10420096

## Citation

> US National Institutes of Health, RePORTER application 10420096, Magnetothermal brain stimulation towards the rescue of beta-amyloid pathology (1R01AG076699-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10420096. Licensed CC0.

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